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To the Editor: Passive exposure to tobacco smoke has been reported to be a risk factor for coronary heart disease (CHD),¹ a relationship that may be mediated by chronic inflammation. Although an increase in memory and total CD4⁺ lymphocyte subpopulations of white blood cells (WBCs) in the blood of smokers has been documented,² and an elevated WBC count is an independent risk factor for atherosclerotic vascular disease,³ a direct association between chronic exposure to passive smoking and immune status remains to be proven. We examined a sample of Japanese men to study the effects of passive and active smoking on lymphocyte subpopulations and WBCs.

Methods
In 1997, we recruited a total of 670 of 783 (85.6%) healthy male workers (mean age, 36 years) in an electric power plant for our study. The plant did not contain any known hazardous chemicals that could affect immunologic function. After providing written informed consent, participants were classified as current smokers (n = 363), former smokers who had quit at least 1 year prior to recruitment (n = 154), or never smokers (n = 153). To determine passive smoking status for former and never smokers, we asked, "Does anyone who is close to you, either at work or at home, smoke cigarettes heavily?" Participants who answered "yes" were classified as passive smokers.

We also assessed age, body mass index, alcohol consumption (1, nondrinker; 2, occasional; 3, average ethanol intake <69 g/d, but not daily; 4, average ethanol intake 69 g/d or more, but not daily; 5, daily drinkers with an average ethanol intake of <69 g/d; and 6, daily drinkers with an average intake of 69 g/day); and frequency of regular exercise (1, not regular; 2, 0-1 time/wk; and 3, 2 times/wk). Blood samples for immune parameters including lymphocyte subpopulations and total WBCs were collected once the questionnaire was completed. We assessed the relationship between smoking status and immune function with multivariate analysis of covariance controlling for the above variables. We used the Scheffé method to compute P values for individual comparisons between groups.

Because our academic institution did not have an institutional review board for epidemiologic studies at the time this study was initiated, our protocol was instead reviewed and approved by the power plant's Committee of Safety and Health, which represented the labor union, workers, the employer, and occupational health staff of the power plant.

Results
Compared with current smokers, the counts of most lymphocyte subpopulations and total WBCs were significantly lower among former smokers and never smokers (Table 1). Among never smokers, however, the counts of most lymphocyte subpopulations and WBCs were significantly higher in those exposed to passive smoking.

View this table: [in this window] [in a new window] Table. Immune Parameters Among Workers According to History of Smoking*

Comment
Passive smoking may be related to an increase in a number of lymphocyte subpopulations. Such immune alteration may accelerate intravascular tissue damage and increase the long-term risk of CHD.

Dr Tanigawa was the corresponding author for this Research Letter.—ED.

Acknowledgment: We thank Ryo Suzuki, MD, DMSc, National Institute of Industrial Health, Japan, for his invaluable suggestions.

Akinori Nakata, DMSc
National Institute of Industrial Health
Kawasaki, Japan

Takeshi Tanigawa, MD, DMSc
Tt9178{at}aol.com
Department of Public Health Medicine
University of Tsukuba
Tsukuba, Japan

Shunichi Araki, MD, DMSc
National Institute of Industrial Health

Susumu Sakurai, DHSc
Department of Laboratory Medicine
University of Tokyo Hospital
Tokyo, Japan

Hiroyasu Iso, MD, DMSc
Department of Public Health Medicine
University of Tsukuba

1. Kawachi I, Colditz GA, Speizer FE, et al. A prospective study of passive smoking and coronary heart disease. Circulation. 1997;95:2374-2379. FREE FULL TEXT 2. Tanigawa T, Araki S, Nakata A, et al. Increase in memory (CD4⁺CD29⁺ and CD4⁺CD45RO⁺) T and naive (CD4⁺CD45RA⁺) T-cell subpopulations in smokers. Arch Environ Health. 1998;53:378-383. ISI | PUBMED 3. Danesh J, Collins R, Appleby P, Peto R. Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies. JAMA. 1998;279:1477-1482. FREE FULL TEXT

Letters Section Editor: Stephen J. Lurie, MD, PhD, Senior Editor.

JAMA. 2004;291:1699-1700.